A Phase ll Study of Neoadjuvant Short-course Radiotherapy Followed by Ivonescimab and Chemotherapy in pMMR/MSS Locally Advanced Rectal Cancer

NCT ID: NCT06919510

Last Updated: 2025-04-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2028-12-01

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of short-course radiotherapy followed by ivonescimab and chemotherapy in participants with pMMR/MSS locally advanced rectal cancer. Patients were randomly assigned to experimental group A or control group B according to a 1:1 ratio. In group A, patients will receive neoadjuvant short-course radiotherapy followed by ivonescimab and chemotherapy. In group B, patients will receive neoadjuvant short-course radiotherapy followed by chemotherapy. After neoadjuvant treatment, the patients and investigator could choose one of the following treatments:(1) Surgery. The patients will receive surgery within 4-8 weeks after the last dose of capecitabine, and the surgical method is selected by the investigator, (2) Watch and Wait (only for patients with clinical complete response after neoadjuvant therapy).

Conditions

Rectal Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A (Short-course radiotherapy followed by ivonescimab and chemotherapy)

Subjects will receive short-course radiotherapy of 25Gy/5 fractions, followed by neoadjuvant chemotherapy of CAPOX and ivonescimab. After neoadjuvant treatment, the patients and investigator could choose one of the following treatments:(1) Surgery. The patients will receive surgery within 4-8 weeks after the last dose of capecitabine, and the surgical method is selected by the investigator: (2) Watch and Wait(only for patients with clinical complete response after neoadjuvant therapy).

Group Type: EXPERIMENTAL

lvonescimab

Intervention Type: DRUG

lvonescimab, DS1, D1,q3w, intravenous infusion

CAPOX (oxaliplatin/capecitabine)

Intervention Type: DRUG

Oxaliplatin 130 mg / m2, D1, intravenous infusion, q3w, Capecitabine 1000 mg / m2,twice a day, oral,1-14 days, then rest for 7 days, q3w.

radiotherapy

Intervention Type: RADIATION

5\* 5Gy, once a day, 5Gy each time, for 5 days

Surgery or watch&wait

Intervention Type: PROCEDURE

The surgical method is selected by the investigator. Watch and Wait (only for patients with clinical complete response after neoadjuvant therapy)

Group B (Short-course radiotherapy followed by chemotherapy)

Subjects will receive short-course radiotherapy of 25Gy/5 Fraction, followed by neoadjuvant chemotherapy of CAPOX .After neoadiuvant treatment, the patients and investigator could choose one of the following treatments:(1) Surgery. The patients will receive surgery within 4-8 weeks after the last dose of capecitabine, and the surgical method is selected by the investigator; (2) Watch and Wait (only for patients with clinical complete response after neoadjuvant therapy).

Group Type: ACTIVE_COMPARATOR

CAPOX (oxaliplatin/capecitabine)

Intervention Type: DRUG

Oxaliplatin 130 mg / m2, D1, intravenous infusion, q3w, Capecitabine 1000 mg / m2,twice a day, oral,1-14 days, then rest for 7 days, q3w.

radiotherapy

Intervention Type: RADIATION

5\* 5Gy, once a day, 5Gy each time, for 5 days

Surgery or watch&wait

Intervention Type: PROCEDURE

The surgical method is selected by the investigator. Watch and Wait (only for patients with clinical complete response after neoadjuvant therapy)

Interventions

lvonescimab

lvonescimab, DS1, D1,q3w, intravenous infusion

Intervention Type: DRUG

CAPOX (oxaliplatin/capecitabine)

Oxaliplatin 130 mg / m2, D1, intravenous infusion, q3w, Capecitabine 1000 mg / m2,twice a day, oral,1-14 days, then rest for 7 days, q3w.

Intervention Type: DRUG

radiotherapy

5\* 5Gy, once a day, 5Gy each time, for 5 days

Intervention Type: RADIATION

Surgery or watch&wait

The surgical method is selected by the investigator. Watch and Wait (only for patients with clinical complete response after neoadjuvant therapy)

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Age between 18 and 75 years;

2. ECOG perfommance status of 0 or 1;

3. Life expectancy: more than 2 years;

4. Histologically proven rectal adenocarcinoma;

5. Tumor biopsy immunohistochemistry proven pMMR, positive for four proteins, MLH1, MSH2, MSH6 and PMS2, or MSS determined by gene testing;

6. According to the 8th Edition of the AJCC Staging Manual, clinical stage cT3-4NanyM0 or cTxN+M0 of II-III rectal cancer was determined by Magnetic resonance imaging (MRI)±transrectal ultrasonography/ ultrasound endoscopy. Lower edge of the tumor was ≤ 12 cm from the anal verge;

7. Eligible for R0 surgery;

8. No prior anti-tumor treatment for rectal cancer,including radiotherapy,chemotherapy, immunotherapy, biologics, small molecule targeted therapy, etc;

9. Adequate organ function;

10. Males or females with reproductive ability who are willing to use contraception in the trial;

Exclusion Criteria

1. Any distant metastasis or inoperable disease, regardless clinical stage;

2. Previous (within 5 years) or concurrent other malignant tumors, excluding those that have been cured;

3. Current presence of gastric intestine obstruction, bleeding or perforation which need emergency surgery;

4. Multiple primary rectal cancers;

5. Previous pelvic or abdominal radiotherapy;

6. Difficulty swallowing;

7. Current presence of uncontrolled combined disease;

8. Active clinical infections;

9. History of severe bleeding tendency or coagulation dysfunction;

10. Presence or history of immunodeficiency; positive for HIV antibodies, current long-term use of systemic corticosteroids or other immunosuppressants;

11. Subjects with known active tuberculosis (TB); suspected active TB should be excluded by clinical examination, known active syphilis infection;

12. Received a live vaccine within 30 days prior to the study, or plan to receive a live vaccine during the study;

13. Local or systemic disease caused by non-malignancy, or disease or symptom secondary to tumor, that can lead to higher medical risk and/or uncertainty in survival;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Akeso

INDUSTRY

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Rui-hua Xu, MD, PhD

President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

AK112-IIT-016

Identifier Type: -

Identifier Source: org_study_id